The main objectives of the proposed research are twofold. The first is to develop fundamentally new cyclization methodologies based on the P.I.'s recent explorations of organotransition metal chemistry. Several intramolecular carbometallation reactions discovered and/or developed over the past several years form a basis for this part of the proposed research. Even now, there are a number of highly desirable chemical transformations that are difficult to achieve by conventional methods. Some such transformations include (i) efficient and selective synthesis of stereodefined exocyclic olefins, and (ii) cyclization, especially asymmetric cyclization, by generation of a quaternary carbon center including stereoselective synthesis of spirocycles. Also highly desirable is construction of bicycles and polycycles via multiple (three or more) carbon-carbon bond formation. It is intended to develop those methodologies which will provide attractive solutions to some of these synthetic problems. Specifically, various types of (i) cyclic acylpalladation, (ii) cyclic carbopalladation, especially multiple ring formation via carbopalladation, (iii) zirconium-promoted bicyclization of enzymes, and (iv) carbometallation of cyclopropenes, especially its asymmetric version, and its application to the synthesis of hydrazulenes will be investigated. The second objective of the proposed study is to apply new methodologies to the selective synthesis of natural or unnatural organic molecules of biological and medicinal interest. This will firstly provide very critical and stringent tests of the newly developed methodologies with regard to their potential synthetic utility. Secondly, some such synthetic endeavors will lead to the development of highly efficient routes to organic molecules of biological and medicinal importance. To these ends, the syntheses of select organic compounds including an antiblood clotting agent, carbacyclin (A-1), frullanolide (A- 2), and antibiotic, nanaomycin A(A-3), daunomycinone (A-4), and antiulcer agent, U-68,215(A-5), and beta-bulnesene (A-6) are planned. Some products as well as intermediates obtained in both exploration and application studies will be submitted to a few organizations for medicinal screening.